Selkoe DJ, Hardy J (2016) The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med 8(6):595–608. https://doi.org/10.15252/emmm.201606210

Article  CAS  PubMed  PubMed Central  Google Scholar 

Martin SJ, Grimwood PD, Morris RG (2000) Synaptic plasticity and memory: an evaluation of the hypothesis. Annu Rev Neurosci 23:649–711. https://doi.org/10.1146/annurev.neuro.23.1.649

Article  CAS  PubMed  Google Scholar 

Bushong EA, Martone ME, Jones YZ, Ellisman MH (2002) Protoplasmic astrocytes in CA1 stratum radiatum occupy separate anatomical domains. J Neurosci 22(1):183–192. https://doi.org/10.1523/JNEUROSCI.22-01-00183.2002

Article  CAS  PubMed  PubMed Central  Google Scholar 

Halassa MM, Fellin T, Takano H, Dong JH, Haydon PG (2007) Synaptic islands defined by the territory of a single astrocyte. J Neurosci 27(24):6473–6477. https://doi.org/10.1523/JNEUROSCI.1419-07.2007

Article  CAS  PubMed  PubMed Central  Google Scholar 

Santello M, Toni N, Volterra A (2019) Astrocyte function from information processing to cognition and cognitive impairment. Nat Neurosci 22(2):154–166. https://doi.org/10.1038/s41593-018-0325-8

Article  CAS  PubMed  Google Scholar 

Simpson JE, Ince PG, Lace G, Forster G, Shaw PJ, Matthews F, Savva G, Brayne C, Wharton SB (2010) Astrocyte phenotype in relation to Alzheimer-type pathology in the ageing brain. Neurobiol Aging 31(4):578–590. https://doi.org/10.1016/j.neurobiolaging.2008.05.015

Article  CAS  PubMed  Google Scholar 

Li K-Y, Gong P-F, Li J-T, Xu N-J, Qin S (2020) Morphological and molecular alterations of reactive astrocytes without proliferation in cerebral cortex of an APP/PS1 transgenic mouse model and Alzheimer’s patients. Glia 68(11):2361–2376. https://doi.org/10.1002/glia.23845

Article  PubMed  Google Scholar 

Nagele RG, D’Andrea MR, Lee H, Venkataraman V, Wang HY (2003) Astrocytes accumulate A beta 42 and give rise to astrocytic amyloid plaques in Alzheimer disease brains. Brain Res 971(2):197–209. https://doi.org/10.1016/s0006-8993(03)02361-8

Article  CAS  PubMed  Google Scholar 

Verkhratsky A, Zorec R, Rodríguez JJ, Parpura V (2016) Astroglia dynamics in ageing and Alzheimer’s disease. Curr Opin Pharmacol 26:74–79. https://doi.org/10.1016/j.coph.2015.09.011

Article  CAS  PubMed  Google Scholar 

Giaume C, Koulakoff A, Roux L, Holcman D, Rouach N (2010) Astroglial networks: a step further in neuroglial and gliovascular interactions. Nat Rev Neurosci 11(2):87–99. https://doi.org/10.1038/nrn2757

Article  CAS  PubMed  Google Scholar 

Decrock E, De Bock M, Wang N, Bultynck G, Giaume C, Naus CC, Green CR, Leybaert L (2015) Connexin and pannexin signaling pathways, an architectural blueprint for CNS physiology and pathology? Cell Mol Life Sci 72(15):2823–2851. https://doi.org/10.1007/s00018-015-1962-7

Article  CAS  PubMed  Google Scholar 

Orellana JA, Retamal MA, Moraga-Amaro R, Stehberg J (2016) Role of astroglial hemichannels and pannexons in memory and neurodegenerative diseases. Front Integr Neurosci 10:26. https://doi.org/10.3389/fnint.2016.00026

Article  CAS  PubMed  PubMed Central  Google Scholar 

Charvériat M, Naus CC, Leybaert L, Sáez JC, Giaume C (2017) Connexin-dependent neuroglial networking as a new therapeutic target. Front Cell Neurosci 11:174. https://doi.org/10.3389/fncel.2017.00174

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mei X, Ezan P, Giaume C, Koulakoff A (2010) Astroglial connexin immunoreactivity is specifically altered at β-amyloid plaques in β-amyloid precursor protein/presenilin1 mice. Neuroscience 171(1):92–105. https://doi.org/10.1016/j.neuroscience.2010.08.001

Article  CAS  PubMed  Google Scholar 

Angeli S, Kousiappa I, Stavrou M, Sargiannidou I, Georgiou E, Papacostas SS, Kleopa KA (2020) Altered expression of glial gap junction proteins Cx43, Cx30, and Cx47 in the 5XFAD model of Alzheimer’s disease. Front Neurosci 14:582934. https://doi.org/10.3389/fnins.2020.582934

Article  PubMed  PubMed Central  Google Scholar 

Pechlivanidou M, Kousiappa I, Angeli S, Sargiannidou I, Koupparis AM, Papacostas SS, Kleopa KA (2022) Glial gap junction pathology in the spinal cord of the 5xFAD mouse model of early-onset Alzheimer’s disease. Int J Mol Sci 23(24):15597. https://doi.org/10.3390/ijms232415597

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cruz NF, Ball KK, Dienel GA (2010) Astrocytic gap junctional communication is reduced in amyloid-β-treated cultured astrocytes, but not in Alzheimer’s disease transgenic mice. ASN Neuro 2(4):e00041. https://doi.org/10.1042/AN20100017

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yi C, Mei X, Ezan P, Mato S, Matias I, Giaume C, Koulakoff A (2016) Astroglial connexin43 contributes to neuronal suffering in a mouse model of Alzheimer’s disease. Cell Death Differ 23(10):1691–1701. https://doi.org/10.1038/cdd.2016.63

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yi C, Ezan P, Fernández P, Schmitt J, Sáez JC, Giaume C, Koulakoff A (2017) Inhibition of glial hemichannels by boldine treatment reduces neuronal suffering in a murine model of Alzheimer’s disease. Glia 65(10):1607–1625. https://doi.org/10.1002/glia.23182

Article  PubMed  Google Scholar 

Madeira D, Dias L, Santos P, Cunha RA, Canas PM, Agostinho P (2021) Association between adenosine A2A receptors and connexin 43 regulates hemichannels activity and ATP release in astrocytes exposed to amyloid-β peptides. Mol Neurobiol 58(12):6232–6248. https://doi.org/10.1007/s12035-021-02538-z

Article  CAS  PubMed  Google Scholar 

Matos M, Augusto E, Machado NJ, Dos Santos-Rodrigues A, Cunha RA, Agostinho P (2012) Astrocytic adenosine A2A receptors control the amyloid-β peptide-induced decrease of glutamate uptake. J Alzheimers Dis 31(3):555–567. https://doi.org/10.3233/JAD-2012-120469

Article  CAS  PubMed  Google Scholar 

Dias L, Madeira D, Dias R, Tomé ÂR, Cunha RA, Agostinho P (2022) Aβ1-42 peptides blunt the adenosine A2A receptor-mediated control of the interplay between P2X7 and P2Y1 receptors mediated calcium responses in astrocytes. Cell Mol Life Sci 79(8):457. https://doi.org/10.1007/s00018-022-04492-y

Article  CAS  PubMed  Google Scholar 

Madeira D, Lopes CR, Simões AP, Canas PM, Cunha RA, Agostinho P (2023) Astrocytic A2A receptors silencing negatively impacts hippocampal synaptic plasticity and memory of adult mice. Glia 71(9):2137–2153. https://doi.org/10.1002/glia.24384

Article  CAS  PubMed  Google Scholar 

Canas PM, Porciúncula LO, Cunha GMA, Silva CG, Machado NJ, Oliveira JMA, Oliveira CR, Cunha RA (2009) Adenosine A2A receptor blockade prevents synaptotoxicity and memory dysfunction caused by beta-amyloid peptides via p38 mitogen-activated protein kinase pathway. J Neurosci 29:14741–14751. https://doi.org/10.1523/JNEUROSCI.3728-09.2009

Article  CAS  PubMed  PubMed Central  Google Scholar 

Viana da Silva S, Haberl MG, Zhang P, Bethge P, Lemos C, Gonçalves N, Gorlewicz A, Malezieux M, Gonçalves FQ, Grosjean N, Blanchet C, Frick A, Nägerl UV, Cunha RA, Mulle C (2016) Early synaptic deficits in the APP/PS1 mouse model of Alzheimer’s disease involve neuronal adenosine A2A receptors. Nat Commun 7:11915. https://doi.org/10.1038/ncomms11915

Article  CAS  PubMed  PubMed Central  Google Scholar 

Faivre E, Coelho JE, Zornbach K, Malik E, Baqi Y, Schneider M, Cellai L, Carvalho K, Sebda S, Figeac M, Eddarkaoui S, Caillierez R, Chern Y, Heneka M, Sergeant N, Müller CE, Halle A, Buée L, Lopes LV, Blum D (2018) Beneficial effect of a selective adenosine A2A receptor antagonist in the APPswe/PS1dE9 mouse model of Alzheimer’s disease. Front Mol Neurosci 11:235. https://doi.org/10.3389/fnmol.2018.00235

Article  CAS  PubMed  PubMed Central  Google Scholar 

Orr AG, Lo I, Schumacher H, Ho K, Gill M, Guo W, Kim DH, Knox A, Saito T, Saido TC, Simms J, Toddes C, Wang X, Yu G-Q, Mucke L (2018) Istradefylline reduces memory deficits in aging mice with amyloid pathology. Neurobiol Dis 110:29–36. https://doi.org/10.1016/j.nbd.2017.10.014

Article  CAS  PubMed  Google Scholar 

Silva AC, Lemos C, Gonçalves FQ, Pliássova AV, Machado NJ, Silva HB, Canas PM, Cunha RA, Lopes JP, Agostinho P (2018) Blockade of adenosine A2A receptors recovers early deficits of memory and plasticity in the triple transgenic mouse model of Alzheimer’s disease. Neurobiol Dis 117:72–81. https://doi.org/10.1016/j.nbd.2018.05.024

Article  CAS  PubMed  Google Scholar 

Orr AG, Hsiao EC, Wang MM, Ho K, Kim DH, Wang X, Guo W, Kang J, Yu G-Q, Adame A, Devidze N, Dubail DB, Masliah E, Conklin BR, Mucke L (2015) Astrocytic adenosine receptor A2A and Gs-coupled signaling regulate memory. Nat Neurosci 18(3):423–434. https://doi.org/10.1038/nn.3930

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lopes CR, Silva JS, Santos J, Rodrigues MS, Madeira D, Oliveira A, Moreira-de-Sá A, Lourenço VS, Gonçalves FQ, Silva HB, Simões AP, Rolo AP, Canas PM, Tomé ÂR, Palmeira CM, Lopes JP, Cunha RA, Agostinho P, Ferreira SG (2023) Downregulation of sirtuin 1 does not account for the impaired long-term potentiation in the prefrontal cortex of female APPswe/PS1dE9 mice modelling Alzheimer’s disease. Int J Mol Sci 24(8):6968. https://doi.org/10.3390/ijms24086968

Article